Many cerebral diseases are associated with abnormal cerebral hemodynamics and impaired cerebral autoregulation (CA). CA is a mechanism to maintain cerebral blood flow (CBF) stable when mean arterial pressure (MAP) fluctuates. Evaluating these abnormalities requires direct measurements of cerebral hemodynamics and MAP. Several near-infrared diffuse optical instruments have been developed in our laboratory for hemodynamic measurements including near-infrared spectroscopy (NIRS), diffuse correlation spectroscopy (DCS), hybrid NIRS/DCS, and dual-wavelength DCS flow-oximeter. We utilized these noninvasive technologies to quantify CBF and cerebral oxygenation in different populations under different physiological conditions/manipulations. A commercial finger plethysmograph was used to continuously monitor MAP. For investigating the impact of obstructive sleep apnea (OSA) on cerebral hemodynamics and CA, a portable DCS device was used to monitor relative changes of CBF (rCBF) during bilateral thigh cuff occlusion. Compared to healthy controls, smaller reductions in rCBF and MAP following cuff deflation were observed in patients with OSA, which might result from the impaired vasodilation. However, dynamic CAs quantified in time-domain (defined by rCBF drop/MAP drop) were not significantly different between the two groups. We also evaluated dynamic CA in frequency-domain, i.e., to quantify the phase shifts of low frequency oscillations (LFOs) at 0.1 Hz between cerebral hemodynamics and MAP under 3 different physiological conditions (i.e., supine resting, head-up tilt (HUT), paced breathing). To capture dynamic LFOs, a hybrid NIRS/DCS device was upgraded to achieve faster sampling rate and better signal-to-noise. We determined the best hemodynamic parameters (i.e., CBF, oxygenated and total hemoglobin concentrations) among the measured variables and optimal physiological condition (HUT) for detecting LFOs in healthy subjects. Finally, a novel dual-wavelength DCS flow-oximeter was developed to monitor cerebral hemodynamics during HUT-induced vasovagal presyncope (VVS) in healthy subjects. rCBF was found to have the best sensitivity for the assessment of VVS among the measured variables and was likely the final trigger of VVS. A threshold of ~50% rCBF decline was observed which can completely separate subjects with or without presyncope, suggesting its potential role for predicting VVS. With further development and applications, NIRS/DCS techniques are expected to have significant impacts on the evaluation of cerebral hemodynamics and autoregulation.

Cerebral autoregulation describes the clinically observed phenomenon that cerebral blood flow remains relatively constant in healthy human subjects despite large systemic changes in blood pressure, dissolved blood gas concentrations, heart rate and other systemic variables. Cerebral autoregulation is known to be impaired post ischaemic stroke, after severe head injury, in patients suffering from autonomic dysfunction and under the action of various drugs. Cerebral auto-regulation is a dynamic, multivariate phenomenon. Sensitive techniques are required to monitor cerebral auto-regulation in a clinical setting. This thesis presents 4 related signal processing studies of cerebral autoregulation. The first study shows how consideration of changes in blood gas concentrations simultaneously with changes in blood pressure can improve the accuracy of an existing frequency domain technique for monitoring cerebral autoregulation from spontaneous fluctuations in blood pressure and a transcranial doppler measure of cerebral blood flow velocity. The second study shows how the continuous wavelet transform can be used to investigate coupling between blood pressure and near infrared spectroscopy measures of cerebral haemodynamics in patients with autonomic failure. This introduces time information into the frequency based assessment, however neglects the contribution of blood gas concentrations. The third study shows how this limitation can be resolved by introducing a new time-varying multivariate system identification algorithm based around the dual tree undecimated wavelet transform. All frequency and time-frequency domain methods of monitoring cerebral autoregulation assume linear coupling between the variables under consideration. The fourth study therefore considers nonlinear techniques of monitoring cerebral autoregulation, and illustrates some of the difficulties inherent in this form of analysis. The general approach taken in this thesis is to formulate a simple system model; usually in the form of an ODE or a stochastic process. The form of the model is adapted to encapsulate a hypothesis about features of cerebral autoregulation, particularly those features that may be difficult to recover using existing methods of analysis. The performance of the proposed method of analysis is then evaluated under these conditions. After this testing, the techniques are then applied to data provided by the Laboratory of Human Cerebrovascular Physiology in Alberta, Canada, and the National Hospital for Neurology and Neurosurgery in London, UK.

Newly created software is presented in magister degree thesis. The software was created for the innovative non–invasive cerebral blood flow autoregulation monitor which has no analogy in the global high tech market. It will be possible at first time to get diagnostic information about the cerebral blood flow autoregulation status of patient with severe brain injuries using such non–invasive monitoring technology in clinical practice. That will help with the individual treatment decision making. Clinical studies were conducted in neurosurgical intensive care units using created software. It has been shown that non–invasive and invasive cerebrovascular blood flow autoregulation monitoring technologies provide the same diagnostic information about the patient status. That conclusion is statistically significant and evidence based. Some R & D projects were performed using non–invasive cerebrovascular blood flow autoregulation monitor with implemented new software. The results of such projects were used in order to formulate the metrological – technological requirements for the final design and development of the innovative non–invasive blood flow autoregulation monitor. Such device is under creation in Telematics Scientific Laboratory which works together with Vittamed Technologijos Ltd and conducts 6.015 million Lt project (BPD04-ERPF-3.1.7-03-05/0020).

Ischaemic stroke is a major cause of death and disability worldwide. Cerebral autoregulation, which can be impaired during acute stroke, and collateral flow to brain tissue through the circle of Willis, both play a role in preventing tissue infarction. The configuration of the arterial circle varies between individuals. Thus, personalised modelling of the cerebral arterial network, to determine the potential for collateral flow, can be of significant value in the clinical context of stroke. The interaction between autoregulation and collateral flow remains poorly understood. In this study, steady-state physiological models of the cerebral arterial network, including several common variants of the circle of Willis, were coupled to a spatially variable mathematical representation of cerebral autoregulation. The resulting model was used to simulate various arterial occlusions, as well as bilateral and unilateral impairment of autoregulation, in each structural variant. The work identified few circle of Willis variants that present either particularly high-risk or particularly low-risk of cerebral ischaemia. Instead it was found that most variants are dependent upon the bilateral function of autoregulation to facilitate collateral flow and preserve cerebral blood flows. When autoregulation was impaired unilaterally, downstream of an occlusion, blood flows in the contralateral hemisphere were preserved at the expense of the ipsilateral tissue at risk. Arterial network models have in the past been personalised using structural, rather than functional, angiography measurements. This thesis presents a novel model-based method for absolute blood volume flow rate quantification in short arterial segments using dynamic magnetic resonance angiography data. The work also investigated the additional information that can be obtained from such functional angiography. The flow quantification technique was found to accurately estimate flows in shorter arterial segments than an existing technique. However, improvements to noise performance, and strategies for rejection of contaminating signals from overlapping vessels within the imaging plane, are required before the technique can be applied to personalised cerebral arterial network modelling.

INTRODUÇÃO: A autorregulação cerebral representa um dos mecanismos fisiopatológicos incertos na hemorragia intracerebral espontânea, cujo comprometimento pode influenciar no resultado prognóstico e terapêutico. O objetivo deste trabalho é avaliar a autorregulação cerebral dinâmica em modelo suíno de hemorragia intracerebral espontânea através do índice de reatividade pressórica cerebrovascular e determinar a eficácia das intervenções clínicas e cirúrgicas. MÉTODOS: Foram estudados 21 suínos híbridos machos com idade de 3 meses. O modelo experimental simulou o efeito expansivo de uma hemorragia intracerebral espontânea de grande volume quando comparado ao cérebro humano. Foram avaliados volumes de expansão diferentes, distribuídos em três grupos com sete suínos cada. O protocolo anestésico incluiu uma monitoração hemodinâmica invasiva associada a preservação da autorregulação cerebral. Os experimentos foram submetidos a monitoração neurológica multimodal e divididos em 5 fases. O índice de reatividade pressórica cerebrovascular estimou a autorregulacão cerebral durante todas as fases, sendo as três primeiras sem intervenções terapêuticas e as duas últimas para avaliar a eficácia das intervenções salina hipertônica e cirurgia. RESULTADOS: Os grupos avaliados foram homogêneos e sem diferença estatística quanto ao comprometimento da autorregulação cerebral comparando os diferentes volumes e tempos de compressão durante as duas primeiras horas da expansão do volume intracraniano. O comprometimento do índice de reatividade pressórica cerebrovascular ocorreu em alguns experimentos influenciando nas fases de tratamento subsequentes, salina hipertônica e cirurgia. CONCLUSÕES: Volumes expansivos elevados podem comprometer a autorregulação cerebral dinâmica e apresentar desfecho terapêutico desfavorável. A intervenção clínica e cirúrgica tem benefício nos experimentos com preservação do índice de reatividade pressórica cerebrovascular / INTRODUCTION: Cerebral autoregulation represents one of the uncertain pathophysiological mechanisms in spontaneous intracerebral hemorrhage, whose impairment may influence prognostic and therapeutic outcome. The aim of this study was to evaluate the dynamic cerebral autoregulation in the swine model of spontaneous intracerebral hemorrhage through the cerebrovascular reactivity index and to determine the efficacy of clinical and surgical interventions. METHODS: Twenty-one male hybrid pigs aged 3 months were studied. The experimental model simulated the expansive effect of a large intracerebral hemorrhage when compared to the human brain. Different volumes were evaluated, distributed in three groups with seven pigs each. Each experiment was divided in five phases. The anesthetic protocol included invasive hemodynamic monitoring associated with the preservation of cerebral autoregulation. Multimodallity monitoring was realised in all experiments. The cerebrovascular reactivity index estimated the cerebral autoregulation during all phases. The first three phases were without therapeutic interventions, and the last two phases were with therapeutic intervention of hypertonic saline solution and neurosurgery respectively. RESULTS: The evaluated groups were homogeneous and without statistical difference regarding the impairment of the cerebral autoregulation comparing different volumes and compression times during the first two hours of the intracranial volume expansion. CONCLUSIONS: Elevated expansive volumes may compromise dynamic cerebral autoregulation and have unfavorable therapeutic outcome. Clinical and surgical intervention had benefit in the experiments with preservation of cerebrovascular reactivity index

INTRODUÇÃO: A autorregulação cerebral representa um dos mecanismos fisiopatológicos incertos na hemorragia intracerebral espontânea, cujo comprometimento pode influenciar no resultado prognóstico e terapêutico. O objetivo deste trabalho é avaliar a autorregulação cerebral dinâmica em modelo suíno de hemorragia intracerebral espontânea através do índice de reatividade pressórica cerebrovascular e determinar a eficácia das intervenções clínicas e cirúrgicas. MÉTODOS: Foram estudados 21 suínos híbridos machos com idade de 3 meses. O modelo experimental simulou o efeito expansivo de uma hemorragia intracerebral espontânea de grande volume quando comparado ao cérebro humano. Foram avaliados volumes de expansão diferentes, distribuídos em três grupos com sete suínos cada. O protocolo anestésico incluiu uma monitoração hemodinâmica invasiva associada a preservação da autorregulação cerebral. Os experimentos foram submetidos a monitoração neurológica multimodal e divididos em 5 fases. O índice de reatividade pressórica cerebrovascular estimou a autorregulacão cerebral durante todas as fases, sendo as três primeiras sem intervenções terapêuticas e as duas últimas para avaliar a eficácia das intervenções salina hipertônica e cirurgia. RESULTADOS: Os grupos avaliados foram homogêneos e sem diferença estatística quanto ao comprometimento da autorregulação cerebral comparando os diferentes volumes e tempos de compressão durante as duas primeiras horas da expansão do volume intracraniano. O comprometimento do índice de reatividade pressórica cerebrovascular ocorreu em alguns experimentos influenciando nas fases de tratamento subsequentes, salina hipertônica e cirurgia. CONCLUSÕES: Volumes expansivos elevados podem comprometer a autorregulação cerebral dinâmica e apresentar desfecho terapêutico desfavorável. A intervenção clínica e cirúrgica tem benefício nos experimentos com preservação do índice de reatividade pressórica cerebrovascular / INTRODUCTION: Cerebral autoregulation represents one of the uncertain pathophysiological mechanisms in spontaneous intracerebral hemorrhage, whose impairment may influence prognostic and therapeutic outcome. The aim of this study was to evaluate the dynamic cerebral autoregulation in the swine model of spontaneous intracerebral hemorrhage through the cerebrovascular reactivity index and to determine the efficacy of clinical and surgical interventions. METHODS: Twenty-one male hybrid pigs aged 3 months were studied. The experimental model simulated the expansive effect of a large intracerebral hemorrhage when compared to the human brain. Different volumes were evaluated, distributed in three groups with seven pigs each. Each experiment was divided in five phases. The anesthetic protocol included invasive hemodynamic monitoring associated with the preservation of cerebral autoregulation. Multimodallity monitoring was realised in all experiments. The cerebrovascular reactivity index estimated the cerebral autoregulation during all phases. The first three phases were without therapeutic interventions, and the last two phases were with therapeutic intervention of hypertonic saline solution and neurosurgery respectively. RESULTS: The evaluated groups were homogeneous and without statistical difference regarding the impairment of the cerebral autoregulation comparing different volumes and compression times during the first two hours of the intracranial volume expansion. CONCLUSIONS: Elevated expansive volumes may compromise dynamic cerebral autoregulation and have unfavorable therapeutic outcome. Clinical and surgical intervention had benefit in the experiments with preservation of cerebrovascular reactivity index